Thirty-six minutes into the closing hour-long run around the streets of the principality, Massa smashed into a barrier as he attempted to turn into Ste Devote at the end of the start-finish straight.
The suggestion was either the throttle jammed open or there was a brake failure as the Brazilian locked up heavily and was unable to turn his car into the corner.
The initial impact into the first barrier was considerable as the front-left of his Ferrari took the full force before the car slid around 100 metres into a TechPro barrier at the run-off area of Ste Devote itself.
It immediately brought out the red flag to suspend the session, which was ultimately held up for six minutes as the car was cleared after Massa had clambered out of the cockpit to walk back to the garage.
It was the catalyst to an error-strewn session because within seconds of the track re-opening, Adrian Sutil lost his Force India on the run up the hill through Massanet, hitting the barriers to his right.
In the final minute, Lotus' Romain Grosjean again lost the back end of his car at Ste Devote.
Clipping a barrier, the left-rear wheel worked loose, the impact pitching him across the track and into more metal that dislodged the right-front.
It was Grosjean's second practice shunt after the Frenchman lost an hour in FP2 on Thursday, when Ste Devote again proved his undoing.
On the timesheet, Grosjean ultimately finished second behind Nico Rosberg who completed a practice clean sweep, posting the quickest lap of the event so far with a one minute 14.378secs.