The second and final rounds of Colosso are similar to the first one, with a few minor differences; there are even more sections of the gauntlet Isaac has to run and the opponent he has to face at the end finishes the puzzles faster. They're also a tougher fight, but that's mitigated somewhat by you reaching the middle and getting the better item first and the fact that you can throw Ragnarok at them to your hearts content.
There are advantages to putting one of your companions in almost all the stages, but some advantages are better then others. Giving Isaac access to the growth psynergy at one point allows him to shave off a little time, but cuts off access to his all important healing spells and Ragnarok.
As long as you're high enough level and have a fair amount of djinn, winning shouldn't be too difficult.
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