Rennes, third in the Ligue 1 standings, suffered their first loss of the season although they made a bright start with a goal by Jires Kembo Ekolo after only four minutes.
The hosts, however, hit back midway through the first half courtesy of an Anthony Knockaert goal and Mohamed Soly and Moustapha Diallo found the back of the net after the interval.
Ligue 1 leaders St Etienne geared up nicely for this weekend's clash at fierce rivals Olympique Lyon by defeating Nice 2-0, their fourth consecutive win in all competitions.
Sochaux were also upset by a third tier side as they lost 2-0 at home to Bastia and Toulouse bowed out with a 2-1 defeat after extra time at Ligue 2 Boulogne.
All clubs involved in European competitions were granted a bye in the third round.
The draw for the last 16 will be made on Tuesday with the final on April 23 at the Stade de France.
