The Mailroom boss mode is a joke hotkey, not a difficulty setting or an unlockable mode. Press Ctrl+B and the boss turns up, praises you with "good work, lizard", hands out a promotion and a pay rise, and then tells you to spend that money on a risky investment or a trip to Vegas.
The Mailroom boss mode: what Ctrl+B actually does
The gag plays out as a short scene with your boss. It ends with you being offered a promotion and a pay increase, and the game expecting you to do something reckless with the money. Nothing about it changes the mail on your desk — it is a gag for the room you are sitting in, not a rule for the shift.
When to use it
It is meant for the situation where you are playing the mailroom at work and somebody walks over to your desk, because the scene is your boss appearing and complimenting you. The trigger sits on your own keyboard, so it works whether or not you are streaming.
If you are setting up a stream rather than working through a shift, the other hotkey features are covered in streamer frog codes, and the rest of the bindings are in controls and settings.