French champions and Ligue 1 leaders Girondins Bordeaux dispatched second division Ajaccio 5-1 in a last 32 match with a hat-trick from Argentine striker Fernando Cavenaghi.
Bordeaux are now on a run of 12 games without defeat - 11 wins and a draw - in all competitions.
In another rescheduled last 64 tie, Ligue 1 bottom club Grenoble won their all-first division tie with second-placed Montpellier 3-2 after extra time thanks to a goal by Nassim Akrour after 104 minutes.
Amateurs Colmar defeated Lille despite being reduced to 10 men in the 94th minute after Cedric Faivre had put the ball into the net with his hand against the third-placed top flight side.
Pape Dieye missed Colmar's third spot kick in the shootout but Tulio de Melo failed to capitalise for Lille.
The goalkeepers, Colmar's Thomas Aupic and Lille's Ludovic Butelle, scored to make it 9-9 before Lille captain Stephane Dumont hit the post and Mezriche converted for the victory.
Mezriche also scored the winner from the spot when Colmar beat second division Metz in a shootout in the previous round.
"At the end of the day, against Metz and against Lille, we have proved we are very strong mentally," Colmar captain Regis Kittler told Eurosport.
"We'll face another Ligue 1 team, Boulogne, in the next round. It will be another game and maybe another feat," he added.
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