If I'm understanding what you're asking, it'd probably be something to the effect of:
Custom expression1:
IF({DE:Custom1}="Red",1,IF({DE:Custom1}="Blue",2,IF({DE:Custom1}="Yellow"),3),0)
Custom expression2:
IF({DE:Custom2}="John",3,IF({DE:Custom2}="Mary",2,IF({DE:Custom2}="Sue"),3),0)
Custom expression3:
IF({DE:Custom1}="Red",1,IF({DE:Custom1}="Blue",2,IF({DE:Custom1}="Yellow"),3),0) * IF({DE:Custom2}="John",3,IF({DE:Custom2}="Mary",2,IF({DE:Custom2}="Sue"),3),0)
So, basically, you just need to repeat the entire expression of each column you want to multiply.