Fourth-tier Yzeure produced an early shock in the Coupe de France last 32 with a 1-0 win over Ligue 1 Lorient.
Cameroon striker Steve Mbida scored the only goal in the 24th minute as Christian Gourcuff's side, who are unbeaten in eight league games, crashed out.
The midfielder, who returned to his first amateur club after ending his professional career in 2011, gave the hosts a 55th-minute lead against Ligue 2 Istres at the stadium in Chasselay bearing his name.
Meanwhile, Rennes and visiting Valenciennes battled to a 1-1 draw, but the hosts dug in to win 8-7 on penalties to advance.
Istres' Cheick Fanta-Mady Diarra forced extra time and ultimately penalties but MDA completed a notable upset when they won the shoot-out 3-2, after Bagaliy Dabo and Benjamin Mas both hit the crossbar for Istres.
Ligue 2 Dijon beat Aubagne on penalties after a 3-3 draw which saw them equalise in the last minute of both normal time and extra time.
Joia Nuno Da Costa put Aubagne ahead in the 15th minute and it was the 80th minute before Brian Babit levelled.
Brahim Dridi appeared to have given the hosts victory in the 87th minute, only for Ousseynou Cisse to hit back two minutes into injury time.
Thierry Batret's 114th-minute penalty was also in vain after a third equaliser from Florin Berenguer and the ensuing shoot-out finished 5-4 in Dijon's favour.
Lens required a comeback in the final ten minutes to see off CFA side Avranches 3-1.
The Mont-St-Michel minnows led through Steven Creac'h but Lens turned the game around through Adamo Coulibaly, Deme N'Diaye and a late own goal from Romain Cabon.
Angers were another team to win on penalties, 6-5 over Chambly after a 1-1 draw, while Cercle Athletique Bastia beat La Roche-sur-Yon 3-0 with all the goals coming in extra time.
Pierre Ruffaut scored twice in Moulins' 6-1 win over Magny Renaissance, Niort won 4-1 at Epinal and Caen beat Pontarlier 3-1.
Saint-Etienne's match at Cannes and the game between Jura Sud and Creteil were both postponed.