Napoli had been favourite to reach the quarter-final stage, but second-half strikes from Enzo Barrenechea, Giuseppe Caso, a Walid Cheddira penalty and Abdou Harroui saw Frosinone record a famous victory.

Walter Mazzarri’s side has endured a turbulent defence of the Serie A championship it secured after a 33-year wait, falling 14 points adrift of leader Inter Milan with just 16 matches played.

But after ending a three-game losing run to secure its place in the knockout stages of the Champions League place with a 2-0 win against Braga, and then recording a 2-1 victory against Cagliari in the league, Napoli will have expected to take a third win on the bounce against a Frosinone side making its debut in the round of 16.

Mazzari made nine changes to the side which beat Cagliari last weekend, while Frosinone boss Eusebio Di Francesco retained only three players from the side that lost at Lecce.

Giovanni Simeone appeared to have given Napoli the lead nine minutes before the interval only to see his goal disallowed by VAR after Jesper Lindstrom was adjudged to have handled the ball in the build-up.

After the interval, Napoli continued to probe for the opener – with Mario Rui’s free-kick striking the woodwork – but the Italian champions were suddenly on the back foot when Barrenechea headed home a corner shortly after the hour mark.

Frosinone then doubled their lead when Giovanni Di Lorenzo’s misplaced pass was intercepted by Caso, who made no mistake in slotting past Napoli goalkeeper Pierluigi Gollini with 70 minutes gone.

The home supporters were left stunned as the six-time winners were suddenly facing up to another early exit from the Coppa Italia after their defeat at this stage of the competition by Cremonese last season.

And it would only get worse for Mazzarri’s men when Matias Soule was fouled by Di Lorenzo in the area with Cheddira, on loan from Napoli, scoring Frosinone’s third of the night from the penalty spot before Harroui netted a fourth deep into stoppage time.

It sealed Frosinone’s first ever win against Napoli, and a quarter-final against either Juventus or Salernitana.