The main thing to remember is that outputs are hard-coded to a channel. Out 1 will output whatever is in channel 1. The inputs are a lot more flexible and can be dropped anywhere inside of a chain, and can even be virtual (e.g. output 1 can be an input somewhere in channel 3).
So in your example lets assume CH 3 & 4 are going to be your stereo output to your sound card or speakers. Set them up as a stereo pair by pressing both channel buttons simultaneously.
Drop a mono mix unit into CH 3/4 chain. In it’s subchain, assign the input to OUT1. This mixer will be your dry mix for CH 1. If you have a wet/dry control on your external FX and want to use that you could optionally skip this step.
Route a cable from OUT1 to your external FX. Route 2 cables from your external FX to IN 1 and IN 2. Drop a Stereo Mix unit into CH 3/4. In that mixer’s subchain, set the inputs to IN 1 and IN 2. This mixer will be your wet level for whatever is generated on CH 1.
Here’s where it starts to get a bit murky for me. It sounds like your external effects are mono in stereo out. Are you just looking to send one side of these (left or right) to the external effects?
You could add additional mixers in the CH 3/4 chain after the two we just added above and put stereo sampler/synth units in them. You won’t be able to route those to CH 1, though. (Technically you could put a mixer on CH 1 and set its input to OUT 3 or OUT 4, but you’ll be creating a feedback loop since CH 1 is already in CH 3/4). So if you need to route these synths/samplers to CH 1 for external processing, you’ll want global chains which you can then use as inputs to mixers on CH 1. I’m not sure you’ll be able to pick one side of a stereo global chain to assign into a mono mixer on mono CH 1 though.