Lyon booked their place in the French Cup last 32 with a 3-1 victory at fourth-tier neighbours Lyon-La Duchere on Sunday, but Toulouse crashed out following a 1-0 loss at National (third-division) side GFCO Ajaccio.
Toulouse became the fifth Ligue 1 club to exit the tournament this weekend, after Brest, Lorient, Sochaux and Caen fell to lower-league opposition on Saturday.
"It's another competition from the championship, but we would still have liked to go through and go as far as possible," said Toulouse coach Alain Casanova.
"We came up against a determined Ajaccio side in an environment that wasn't easy, particularly in terms of the pitch."
Lyon were indebted to talismanic striker and captain for the day Lisandro Lopez, who netted a first-half hat-trick to take Remi Garde's side a step closer to ending the club's four-year trophy drought.
Carlo Ancelotti will oversee his first competitive game as Paris Saint-Germain coach later on Sunday, when his new club visit fifth-tier Saint-Colomban Locmine.
As Locmine's Pigeon Blanc stadium in Brittany only seats 450 spectators, the game is being played at Lorient's Stade du Moustoir.
Brest fell 2-0 at current National leaders Niort on Saturday, while Caen, Lorient and Sochaux all went down to teams from Ligue 2.
Sochaux were beaten 4-1 by Bastia, Lorient were undone by an 80th-minute Yohann Riviere goal in a 4-3 defeat at Le Havre and Caen lost 4-2 to Troyes despite having fought back from two goals down to take the game to extra time.
Auxerre required a Dariusz Dudka penalty three minutes from the end of extra time to see off valiant fifth-division Chambly 1-0, while there were also wins for top-tier sides Nice, Dijon, Ajaccio and Evian-Thonon-Gaillard.
Lille begin their defence of the trophy with an emphatic 6-0 success at sixth-division minnows Chantilly, in which on-loan Liverpool midfielder Joe Cole claimed the first senior hat-trick of his club career.
In one of the round's most intriguing ties, Marseille won 5-0 against five-time cup winners Red Star -- currently residing in the third tier -- in a game that took place at Stade de France.
In the only all-Ligue 1 ties of the round, Rennes eased past Nancy 3-0 and Bordeaux beat Saint-Etienne 4-2 on penalties after the game finished 1-1 following extra time.
Source: AFP
