Cone cartridges and virtually all 3rd party cartridges for the Epson R3000 must be primed before using in your printer. The priming process insures that air is removed from the interior channels in the cartridge. Cone provides easy instructions for priming. It is critical that you do not run the Cone cartridges until they are completely empty. If you do you will lose the cartridge priming and will have to reprime the cartridges. Most importantly, you may get air into the ink tubes that run from the cartridges to the printer head. If this happens the air in the ink tubes will be very difficult to remove and will probably require many head cleaning cycles, wasting a considerable amount of expensive ink.
With refilling your cartridges, there is no advantage to running a cartridge dry. With my printers, when a cartridge registers low, I refill all the cartridges in the printer at the same time.
Bob