1. When somebody has taken advantage of your good nature for the last time.

2. When somebody has repeatedly taken the piss, disrespected or insulted you, or somebody close to you, to the point that you no longer wish to associate with them.
Doreen: "How come you don't speak to them anymore?"

Margery: "Fuck them, they've shit their hole full."
by the pious bird of good omen February 25, 2017
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