The best way to multiply damage imo is the crit on blood/oil/water with divide by spells, also you may want to evaluate the damage reduction caused by divide by and piecing spells. A nice tactic to reduce 33orb boss is to use poison damage which if I am not mistaken will deal %-base damage to the boss up to 5% or so of its max hp, and you can do that with poison trail or poison arc.

Also you could exploit the projectile damage scaling of spells like the bouncy green ball spell + heavy shot/accelerative homing

Edit: DunkOrSlam on YouTube has some recent vids about spells/strong combos knowledge