Guingamp, who put relegation concerns aside last season to win the 2014 showpiece at the expense of Rennes, were drawn against Yzeure in January following their respective victories.
The Coupe de France holders saw off Ligue 2 side LB Chateauroux 2-0 in the round of 32, while Yzeure upstaged second division team Valenciennes by the same scoreline.
Guingamp are yet to face Ligue 1 opposition en route to the last 16 as they prepare for Wednesday's trip to Stade de Bellevue but Jocelyn Gourvennec's men head into the fixture full of confidence following Sunday's impressive 1-0 win at home to Monaco.
"Our victory was a huge accomplishment because it was a very strong team we were up against anyway, never mind playing 10 against 11," Gourvennec said afterwards.
"We lost to them in the Coupe de la Ligue three weeks ago. Despite that result, losing a man in that game showed us that we could against them 10 against 11.
"I think Monaco struggled, even though they had some chances and Jonas [Lossl] made some really important saves."
Also in action on Wednesday are eight-time winners Paris Saint-Germain and Monaco.
PSG will host fellow top-flight side Nantes for a spot in the quarter-finals after accounting for Bordeaux 2-1 last time out.
While PSG have swept almost all before them in recent years - winning two Ligue 1 titles, two Trophee des Champions trophies and the Coupe de la Ligue - the Coupe de France has proved elusive for the capital club.
Since winning the 2010 final against Monaco after extra time, PSG have only managed to reach the decider once, losing to Lille the following year.
PSG's form leading into Wednesday's match at Parc des Princes is strong, having won three of their past four fixtures in all competitions, which includes Sunday's 1-1 draw at Ligue 1 leaders Lyon.
"We deserved to win tonight, but luck wasn't on our side. We played well. We played some good football," PSG midfielder Blaise Matuidi said on Sunday.
"We were up against an excellent goalkeeper and he should be congratulated. We didn't do what we needed to do to open the scoring."
Ligue 1 pair Monaco - winners of the tournament on five occasions - and Rennes will go head-to-head at Stade Louis II.
Saint-Etienne are the only Ligue 1 representative in action on Tuesday.
Christophe Galtier's Saint-Etienne are away to third-tier Red Star.
Elsewhere on Tuesday, Boulogne entertain Quevilly, Auxerre travel to Le Poire-sur-Vie and Iris Club de Croix do battle with Concarneau.
Metz and Brest conclude the last-16 fixtures on Thursday.
