Fourth-tier Grenoble caused a massive shock in the last 64 of the Coupe de France after they beat Marseille 5-4 on penalties at home after it finished 3-3 after extra-time.
Mourad Nasrallah netted the winning penalty for Grenoble after Selim Bengriba netted a last-gasp equaliser for the hosts.
Andre Pierre Gignac had struck twice for OM in normal time but they were twice pegged back thanks to strikes from Mourad Nasrallah and then Fares Hachi.
Ayew thought he won the game for Marseille in the 98th minute before Bengriba levelled again late on.
St Etienne needed extra-time to secure a 1-0 win over Nancy from Ligue 2, with Franck Tabanou scoring the only goal in the 97th minute.
In an all Ligue 1 clash, Bordeaux were 2-1 winners over Toulouse thanks to goals from Thomas Toure and and Abdou Traore, with Wissam Ben Yedder netting the visitors' consolation.
Lens fought back well from three goals down but came up short as they lost 3-2 to Lyon, who went ahead through Nabil Fekir, Alexandre Lacazette and Mouhamadou Dabo before Lyon struck back through Alharbi el Jadeyaoui and Adamo Coulibaly.
Monaco beat Nimes 2-0 thanks to goals from Bernardo Silva and Valere Germain, while Guingamp were 3-0 winners at Dinan-Lehon and Rennes beat Dunkerque 2-1.
Yzeure won 3-1 at Pagny Sur Moselle, Metz beat Epinal 2-1 while Consolat Marseille beat Ajaccio 3-0.
Cholet needed penalties to beat Beauvais after the game finished goalless after 120 minutes, Dijon beat Caen 3-2 and Auxerre beat Strasbourg 1-0.