You will be fine running 2 per channel even if underpowered. I know the iNuke 3000 puts out less than the EP4000, but try it first before buying another amp. You have nothing to lose. I started with 2 SI HT 18 D2's (4.0 cu ft sealed / wired into 4ohm) off an EP4000 and noticed a nice upgrade when going to 4 18's (2ohm per channel). Gaining around 300RMS each and the extra displacement made a nice noticeable difference. I think this would keep a lot of people happy. When I feed all 4 @ 650RMS each I noticed another nice step up.
I now run 8 D2's off 2 EP4000's, They see a bit less then 500RMS each and absolutely punish my home and move the cones nicely excursion wise (during low Hz).
^Those are give or take tested watts. Not the inflated watts Behringer rate their amps at.
I tested things in a 3600 cu ft open L-shaped basement. My personal opinion is you should have more firing power for a 6000 cu ft room. Especially if you don't have the low frequency reinforcement concrete basements offer.
Since you want the lowest frequency, multiple sealed and lots of watts! If that's beyond your budget, start with 4 18's in HUGE ported enclosures.
BTW: If Infinite Baffle is possibility you would save a bunch of $ not needing box materials. Not to mention you only need a fraction of power! More $avings
Testing is order to know if the location provides a good frequency response at you your listening position. Nothing like nulls taking all the fun out of it. I hate hearing about Integration problems after installs.
Multiple sealed boxes are great because you can easily move them around your room and naturally flatten frequency response. I can fit my 4.0 cu ft boxes in a lot of locations.