The competition often provides an array of shocks and holders Lille and Girondins Bordeaux narrowly avoided joining their Ligue 1 counterparts on the Cup scrapheap.
Four-times winners Auxerre were humbled 2-1 at home by second-tier Chateauroux, who triumphed thanks to a two-minute double from Maxime Bourgeois just after the half-hour mark.
Fourth-division Bourg-Peronnas beat Ligue 1 bottom side Ajaccio 3-2 after extra-time.
Lille were given a mighty scare against fourth-tier Compiegne before Bruno Gianni's goal after 114 minutes sealed a 1-0 extra-time win.
Last season's league and cup double winners laboured against their north eastern neighbours and Compiegne almost pulled off a shock but Hubert Aulon's second-half drive grazed the bar.
Lille, who had lost their last two matches, put out an almost full strength side but struggled on a tough pitch in heavy rain in Beauvais where tiny Compiegne opted to play the home tie.
"What counts in the cup is going through. To go far in the cup you sometimes have to get through via the back door," Lille coach Rudi Garcia told reporters.
Bordeaux needed a 4-3 penalty shootout win to overcome third-division Creteil-Lusitanos after a 2-2 away draw.
Top-flight Dijon beat Ligue 2 Istres 2-1, Evian eased to a 2-0 win at fourth-league AS Valence and Stade Rennes won the Ligue 1 battle with Nice 5-4 on penalties after a goalless draw.
Paris Saint-Germain won 4-0 at lower league Sable sur Sarthe on Friday. The remaining last 32 games follow on Sunday and Monday.
