There is a bug, still in the current version of DspMixFX or the firmware.
Often DspMixFX will recognise the UR44 is connected and show the faders etc,
and your DAW will function,
but DspMixFX will not properly follow/control what is happening in hardware.
I was having the same problem - DI track set to line out 3, other tracks set to main outs.
Everything in DspMixFX muted and faders down, except DAW and Master in Mix1 and Mix2.
DAW Main mix set to output to UR44 Mix1L+R only.
DI track set to UR44 Mix2L (and thus Lineout 3)
Try to reamp - squeal.
Listening to Lineout 3 with headphones - it was not silent with nothing playing, all inputs dead/muted and DAW closed.
I could hear the hiss of an unmuted channel of some sort.
(Lineout 1/2 are dead silent through headphones when nothing playing).
Something was still making it through to Mix2.
insert confused face 
- this doesn’t correspond to what I’ve set up.
Playing around with other tracks in the daw while listening to lineout3 with headphones, I determined I could still hear the main mix (set to Mix1 L+R in my DAW) coming through.
I noticed the the phantom power indicator in DspMixFX was off, despite it being on in hardware (switch on the UR44).
After unplugging the UR44 a few times and closing/reopening DspMixFX it regained control/sync with the hardware and suddenly feedback was gone and reamping worked as expected.
And at this time the Phantom power indicators in DspMixFX also came on, matching the hardware.
The guy above is not confused. On at least some systems some of the time, the UR44/software is not behaving. There is a bug here.
But, once you get it set up and kick it a few times it works and you don’t have to touch DspMixFX.
Over to you steinberg to acknowledge.
For anyone who wants to know exactly what to set in DspMixFX:
All Inputs muted in Mix1 and Mix2 (this is “No direct monitoring”)
DAW and Master UNmuted in Mix1 and Mix2
All Faders at 0dB
Rev-X send on in Mix1 so it is off in Mix2 (doesnt matter too much, just being complete)
Rev-X reverb TIME and RTN all the way down.
Set headphone 2 on in Mix2. You should be able to hear the DI track nicely by itself thru Phones2 output, while the rest of the mix plays through your monitors (Main Outs).
When you stop playback, you should hear silence, not tape hiss. If you hear tape hiss - yank the usb cable and restart DspMixFX repeatedly until it does what its told and then leave it alone.