Mauro Icardi netted a hat-trick as the home side registered their first Serie A win of the season, with Mateo Kovacic, Fredy Guarin and a Pablo Daniel Osvaldo brace accounting for the rest of the goals at San Siro.
The result came almost exactly a year after Inter beat Sassuolo by the same scoreline on the road last season.
And Di Francesco, whose side drew 1-1 at home to Cagliari in their opening league fixture, was quick to declare his bemusement at the display.
"I am asking myself how this could have happened," he is quoted as telling Cielo. "In the space of a week we went from the stars to the gutter.
"We simply did not look like a team fighting for safety as we were not determined enough.
"I can't explain it and there's huge regret because I didn't expect a performance like this.
"I would have gladly made 11 changes today.
"In the first half Kovacic made the difference and we didn't limit him at all. If we analyse the whole 90 minutes, we got everything wrong.”
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