Nowhere near enough info, how many units, what size, appx square foot of each floor, hard duct mains or all-flex system, would be a start.
A 6" flex carrying the same cfm's of air as an 8" will have a higher velocity but will also need an increase in static pressure to accomplish, there-by creating a problem with the design of the rest of the system.
A 6" flex will carry appx 225 cfm's at the Trane recommended max (for residential) of 1200 feet per minute.
An 8" will carry appx 420 cfm's to carry 420 cfm's in a 6" flex you would need appx 2400 feet per minute FPM which is twice as much as the average residential design will allow (getting on for nearly 2.0 static) which a standard a/c system cannot produce.
12X13 is borderline 1 @ 6". any larger would be 2@7'. Two windows in the room would bump it up to two as would a skylite. This is with refrigerated air. Evaporative cooling would require boosting duct size to 7".
I am in a moderate climate (Albuquerque). A harsh climate could change things as could a more moderate climate.
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