What do 3-digit reference designators mean?

You should be able to figure out it looking at the device as whole. You can find such numbering in the devices with multiple boards, multiple physical or logical blocks in it. First digit may designate block #, other two (usually) designate component # in the block.

Often, in multi-channel circuits (same circuit repeated several times), the first digit will indicate the channel, while the remaining digits indicate the specific component. For example, R101, R201, R301... will each be the "same" component, but in channels 1, 2, 3...

I personally usually use 4 digits: first two are the sheet number and last two are the unique number for this component. That means I can use up to 99 components of each type on each sheet! Of course sheets 1-9 have 3-digit reference designators.

I suspect this or something similar is the reason you see 3-digit numbers.

I find this method quite convenient especially during layout. When you are in the process of placing components, this is a good way of more or less knowing where does each component belong to.