Vincent Bessat's hat-trick sent Ligue 1 leaders Lyon out of the Coupe de France on Tuesday, while fourth-tier Quevilly also progressed.
Bessat's stunning treble helped Nantes beat Lyon 3-2 in the only all-Ligue 1 clash of the day.
The 29-year-old midfielder, who scored just once in 2014, picked an ideal occasion to fire as he sent Nantes into the competition's last 16.
With 20 Ligue 1 goals already this season, Lyon's Alexandre Lacazette has clearly been the division's standout forward.
And he carried his form into the French cup competition with a fifth-minute strike for the travelling side.
But Hubert Fournier's side were derailed by two Bessat strikes in the space of three first-half minutes.
Nabil Fekir levelled in the 59th minute for Lyon, but Bessat's 89th-minute effort sealed his hat-trick and Nantes' progression.
Quevilly shocked Ligue 1 outfit Bastia on penalties after the two sides were locked at 1-1 after 120 minutes.
Neither side could score in the first 90 minutes but Bastia seemed on the verge of progression when Djibril Cisse netted.
Cisse's 107th-minute strike was cancelled out by Adama Sarr, though, and Quevilly took the momentum into the penalty shootout.
There was no such drama for Ligue 1 Metz, who beat Avranches 3-0 - although all three goals did come in extra time. Avranches finished the match with 10 men.
Fourth-tier sides Yzeure and Concarneau booked their spot in the next round as well.
Yzeure beat Ligue 2's Valenciennes 2-0, while Concarneau also ousted a second-division side, defeating Dijon 1-0.
Elsewhere, Auxerre beat Jura Sud 1-0 while Iris Club de Croix edged Andrezieux 2-1.
