Chambery's French Cup fairytale came to an end on Wednesday when they were defeated 3-0 by second tier Angers, while holders Paris Saint-Germain edged Le Mans 2-0 in extra time to reach the semi-finals.
They were joined later by Lille, who kept alive their hopes of a domestic double as the Ligue 1 leaders edged fellow Ligue 1 side Lorient 5-3 on penalties after the match ended 0-0 after extra-time.
Fifth-tier Chambery, who had previously eliminated Ligue 1 sides Sochaux, Brest and Monaco, fell behind in the 45th minute at Grenoble's Stade des Alpes when Henry Saivet converted a left-wing cross from Yves Deroff.
Angers, victors against top-flight Bordeaux in the last 32, made it 2-0 just after the hour when Sebastien Renouard pounced on a Gaetan Charbonnier free-kick at the back post.
Charbonnier's replacement, Diego Gomez, completed victory six minutes from time as Chambery's dreams of reaching Stade de France finally disintegrated.
"I'm proud of my players and what they accomplished," said Chambery coach David Guion. "We can have no regrets, even though the score was a bit heavy. It shone a big spotlight on our club, Chambery, and the Savoie region."
It is the first time Angers, currently 11th in France's second division, have reached the last four in the cup since 1969.
"We're one match from Stade de France," said Angers coach Jean-Louis Garcia. "It's fantastic for a Ligue 2 club. We're looking forward to the draw and hoping to play at home."
Goals from teenage substitutes Jean-Christophe Bahebeck, 17, and Neeskens Kebano, 18, gave PSG a hard-earned victory at Parc des Princes, in a match that saw both sides finish with 10 men.
Le Mans spurned a glorious opportunity to take the lead in the 19th minute when Idir Ouali saw a penalty pushed away by PSG goalkeeper Gregory Coupet after Fousseyni Cisse had been felled by Zoumana Camara.
Camara was cautioned for his transgression and he was sent off with 12 minutes of normal time remaining for an ugly studs-up foul on an opponent.
Le Mans enjoyed a numerical advantage only until the first minute of the extra period, however, when centre-back Mamadou Wague picked up his second yellow card of the evening.
Bahebeck gave PSG the lead in the 109th minute when he drilled in at the near post following a short corner with Nene, before Kebano tapped home from Marcos Ceara's centre to seal the holders' place in the last four.
"My players were superb and the youngsters finished the work of the older guys," said PSG coach Antoine Kombouare.
"It's a nod to our academy and the coaches who do such a great job there."
Top-tier Nice became the first side to reach the last four when they defeated second-division Reims 3-2 on Tuesday.
Reims, two-time European Cup runners-up in the 1950s, twice pegged the visitors back before Gabonese forward Eric Mouloungui settled the tie in extra time with his second goal of the game.