Goals from Sam Austin, Macaulay Langstaff (2) and Jodi Jones couldn't prevent defeat on a dramatic day at the JobServe Community Stadium.
Austin had pulled us level on 22 minutes, cancelling out Liam Chilvers' opener, only for Jayden Fevrier and Arthur Read to send the hosts into half-time 3-1 ahead.
Langstaff pulled a goal back immediately after the restart before Cameron McGeehan made it 4-2.
Jones then gave us fresh hope, only for Read to score his second screamer of the game with 15 minutes to play.
McGeehan saw red with 10 minutes of normal time remaining and, inside 10 added minutes, Langstaff got his second to make it 5-4.
But that proved to be the end of the scoring as we left Essex empty-handed.
Luke Williams made one change to the side that overcame Forest Green Rovers in a seven-goal thriller last weekend, John Bostock dropping to the bench and Aaron Nemane returning to the starting XI following a one-match ban.
That meant Austin swapped right wing-back for a more central role along with Matt Palmer, Dan Crowley and David McGoldrick.
Jones and Nemane looked to supply Langstaff from out wide, with Kyle Cameron, Richard Brindley and Aden Baldwin providing goalkeeper Aidan Stone’s last line of defence.
After controlling the early possession, we conceded the first big chance of the game when, on six minutes, Baldwin had to make a big block to keep Samson Tovide’s six-yard effort out after he’d received a low cross from the right.
And we were behind four minutes later when Stone misplaced a pass into midfield, allowing Chilvers to guide the ball into his empty net from 40 yards.
We issued a bright response, Crowley’s excellent cross somehow evading everyone in the middle before, a few minutes later, McGoldrick could only shoot into the body of Langstaff after Nemane had bundled his way into the area.
It didn’t take too much longer for us to draw ourselves level – and it came courtesy of an incisive piece of play from Crowley, who threaded Langstaff into the area. The Teessider’s shot was saved but Austin was first to the rebound, turning the ball home.
We were kicking ourselves six minutes later, though, as we weren’t able to halt Fevrier’s weaving run into the area and could only watch on as the right back’s low shot nestled in the net.
Again we set about a quick response, working an opportunity for Langstaff to send an overhead kick goalwards. He couldn’t connect properly, though, and the hosts launched a counter attack which resulted in Cameron heading a shot off the line after Stone had done well to save the initial effort.
The game was wide open at this stage and we had Brindley to thank for another important block, this time denying Joe Taylor, as Colchester hit us on the counter once again.
And, two minutes later, we found ourselves behind when Baldwin was adjudged to have a fouled his man 20 yards out despite appearing to have cleanly taken the ball. Read took charge of the free-kick, bending it beautifully into the top corner.
Crowley had a half-chance to reduce the deficit shortly before the break, controlling a half-cleared cross in the area but blazing the ball high and wide.
And, after McGoldrick had cut in from the left and curled an effort narrowly wide of the far post, the referee called time on an eventful first half.
Bostock replaced Austin at the interval and we made a purposeful start to the second period, giving the 925 travelling Magpies hope of a comeback.
And those hopes were boosted massively on 48 minutes when Palmer’s half-cleared cross dropped for Cameron, whose volley was turned into the net instinctively by Langstaff six yards out.
A big chance to equalise then passed us by as we broke four-on-two. Nemane could perhaps have played Langstaff through initially, but instead he played the ball wide for Palmer. If he’d have found the right pass, Jones would have had time to compose himself for the finish – but he put just too much on the ball and it ran out for a throw.
And, a minute later, we were rueing that missed opportunity as Baldwin underhit a pass back to Brindley, allowing the hosts to reclaim possession and square the ball for McGeehan to tap into an empty net.
A double change followed as Palmer and Nemane made way for O’Brien and Adebayo.
And, after Owen Goodman had made a good low save to keep Langstaff’s header out, we gave ourselves another lifeline when Jones worked his way past two defenders down the left before curling a stunning effort into the far top corner.
Again, though, we couldn’t make out momentum count before conceding again as Read scored his second sensational goal of the game – this time a rocket after he received the ball in space 25 yards out.
McGoldrick headed a Crowley cross over and a Colchester defender sent a panicked header just over his own bar as we refused to give up on the game.
And our chances of a miraculous comeback were given a boost by a second yellow card for McGeehan, who was sent for an early bath after remonstrating with the referee.
McGoldrick and Bostock both sent long-range efforts off-target shortly before 10 minutes of added time were indicated.
In the first of those, McGoldrick bent an effort just wide of the far post – but within seconds we’d halved the deficit once again as Jones stood up a delightful cross for Langstaff to nod into an empty net.
The pressure was incessant and it could have resulted in an equaliser three minutes later when the ball dropped for Cameron with his back to goal in the area. He couldn’t connect properly with his right-footed effort on the turn, though, and our final big chance of the game was gone.
STARTING XI: Stone; Cameron, Brindley, Baldwin; Jones, Nemane (Adebayo 61'); Palmer (O'Brien 61'); McGoldrick, Austin (Bostock 46'), Crowley; Langstaff
SUBS: Slocombe, Rawlinson, Chicksen, Randall
BOOKINGS: McGoldrick 16', Baldwin 37', Cameron 54'
ATTENDANCE: 4,389 (925)