Fourth-tier Yzeure produced an early shock in the Coupe de France last 32 with a 1-0 win over Ligue 1 side Lorient.
Cameroonian 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.
Yzeure's CFA rivals Monts d'Or Azergues also enjoyed an upset win, inspired by their former France international Ludovic Giuly.
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.
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 10 minutes to see off CFA side Avranches 3-1.
The Mont-St-Michel minnows led through Steven Creac'h (53) but Lens turned the game around through Adamo Coulibaly (81), Deme N'Diaye (84) 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.
St Etienne's match at Cannes and the game between Jura Sud and Creteil were both postponed.
In the pick of the later kick-offs, Rennes won their all-Ligue 1 tie against Valenciennes 8-7 on penalties after a 1-1 draw.
Mathieu Dossevi drew the visitors level after Julien Feret's penalty gave Rennes the lead, but defender Gary Kagelmacher missed with Valenciennes' first attempt in the shoot-out.
Nelson Oliveira's miss set up sudden death and it was 7-7 after eight penalties each, before Marco Da Silva hit the crossbar and Tiemoue Bakayoko won it for Rennes.
Toulouse needed a stoppage-time strike from Martin Braithwaite to edge past lowly Romorantin 2-1.
Adrien Regattin's opener was cancelled out in the 86th minute by Audrick Linord but there was heartbreak for the CFA side as Danish striker Braithwaite scored in the 94th minute.
Sochaux had a more comfortable evening, winning 3-0 at Bressuire. Papa Camara scored twice to add to Sanjin Prcic's opener.
Third-tier Boulogne beat Beauvais 3-1 with an Alhassane Keita brace and CFA pair Plabennec and Concarneau had 1-0 wins away to Les Herbiers and Poissy respectively.